Go Totsukawa / Tokyo Metropolitan University, 2020
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Japanese scientists have found that a mutation in the gene for the MARK4 protein makes its structure more sticky and that is why it is more likely to accumulate in the brain. This ultimately leads to Alzheimer’s disease. About opening is told at Journal of Biological Chemistry.
Today, Alzheimer’s disease affects tens of millions of people around the world. According to the World Health Organization, it is currently the most common cause of senile dementia. It is expected that if an effective cure for this disease is not found soon, the number of cases worldwide will double every 20 years.
Alzheimer’s is believed to be caused by the accumulation and formation of large clumps of tau protein in the brain. These sticky aggregates cause the death of neurons, which leads to memory impairment, impairment of motor functions, and subsequently to death of a person. To date, the exact reason why the tau protein suddenly begins to accumulate in the cells of patients with Alzheimer’s disease has not been established. A detailed understanding of the mechanisms of the formation of this “cellular debris” can help in the development of new therapies and prevent the development of disease.
Researchers at the University of Tokyo, led by Associate Professor Kanae Ando, have discovered the likely cause of the development of a pathological condition of the brain, which is usually associated with the development of Alzheimer’s disease. They studied the role of the MARK4 enzyme (kinase 4, which regulates affinity for microtubules) in the development of the disease. Normally, tau protein is an important part of the structure of the cell and its cytoskeleton. In order for the end sections of the microtubules to be constantly disassembled and re-lined up, it is necessary that the tau protein detaches from them in time. It is the MARK4 enzyme that helps the tau protein to do this.
However, if the gene that makes the normal MARK4 protein carries a mutation, problems begin. Scientists were able to make pinpoint changes in the genome of transgenic fruit flies, which, among other things, produces human tau protein. As a result, it was possible to trace in vivohow the broken MARK4 enzyme alters the tau protein, creating its abnormal form. Under the influence of the mutant form MARK4, an excessive amount of certain chemical groups (phosphoric acid residues) appears on the tau protein, which causes it to fold into an irregular shape. This “bad” tau protein accumulates much more easily in the form of dense clots, can no longer be dissolved by detergent substances and as a result causes neurodegeneration.
–Degrees of tau protein aggregation upon conjugated expression of various types of damaged MARK4 enzyme
Kanae Ando et.al / JBC, 2020
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The researchers also found that breakdowns in the MARK4 enzyme gene can cause a fairly wide range of other diseases that are associated with the accumulation and aggregation of other proteins within nerve cells. That is why studies of this protein and its interactions with cellular structures will help in the development of new treatments for a wide range of neurodegenerative diseases.
Previously, a large number of possible causes were suspected of increasing the risk of developing Alzheimer’s disease. For example, suspicions fell on herpes virus, on wrong lifestyle or on bacterial etiology development of the disease. The proposed methods of treatment for a dangerous ailment are also interesting. For instance, here you can read about how micro doses of LSD can help fight disease.
Alexey Kozlov
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